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https://www.readbyqxmd.com/read/29667118/acmt-position-statement-alternative-or-contingency-countermeasures-for-acetylcholinesterase-inhibiting-agents
#1
Andrew Stolbach, Vikhyat Bebarta, Michael Beuhler, Shaun Carstairs, Lewis Nelson, Michael Wahl, Paul M Wax, Charles McKay
First responders and health care providers must prepare to provide care for patients poisoned by acetylcholinesterase (AchE) inhibitor chemical warfare agents or pesticides. However, pre-deployed medical countermeasures (MCMs) may not be sufficient due to production and delivery interruption, rapid depletion of contents during a response, expiration of MCM components, or lack of local availability of approved MCMs. To augment supplies of community-based and forward-deployed nerve agent countermeasures, the American College of Medical Toxicology (ACMT) supports several strategies: (1) The use of expired atropine, diazepam, and pralidoxime auto-injectors and vials if non-expired drugs are unavailable; and (2) Investigation, development, and identification of alternative countermeasures-commonly stocked drugs that are not approved for nerve agent poisoning but are in the same therapeutic class as approved drugs...
April 17, 2018: Journal of Medical Toxicology: Official Journal of the American College of Medical Toxicology
https://www.readbyqxmd.com/read/29577198/study-of-the-oxime-induced-reactivation-of-acetyl-and-butyrylcholinesterase-of-human-with-inhibition-of-organophosphorus-insecticide-in-vitro
#2
A M Kolesnikov, M A Yuidin, A S Nikiforov, I M Ivanov, N G Vengerovich, A S Makacheev
The efficiency of different reactivators of cholinesterase (toxogonin, dipiroxime, pralidoxime, carboxim, HI-6, and methoxime) at inhibition of butyrylcholinesterase and human acetylcholinesterase by organophosphate insecticide malathion was evaluated in in vitro experiments. Most reactivators increased inhibition of butyrylcholinesterase in comparison with the control, but HI-6 in a concentration of 10-3 mol/liter partially (10%) restored activity of the enzyme. Oxime-induced reactivation of acetylcholinesterase was most pronounced in dipyroxime and toxogonin: parameters of the kinetics of reduction of the phosphorylated enzyme differed by more than 2 times from the values received with the use of other reactivators...
March 26, 2018: Bulletin of Experimental Biology and Medicine
https://www.readbyqxmd.com/read/29467029/a-newly-developed-oxime-k203-is-the-most-effective-reactivator-of-tabun-inhibited-acetylcholinesterase
#3
Kamil Kuca, Kamil Musilek, Daniel Jun, Jana Zdarova-Karasova, Eugenie Nepovimova, Ondrej Soukup, Martina Hrabinova, John Mikler, Tanos C C Franca, Elaine F F Da Cunha, Alexandre A De Castro, Martin Valis, Teodorico C Ramalho
BACKGROUND: Based on in vitro and in vivo rat experiments, the newly developed acetylcholinesterase (AChE) reactivator, K203, appears to be much more effective in the treatment of tabun poisonings than currently fielded oximes. METHODS: To determine if this reactivating efficacy would extend to humans, studies were conducted in vitro using human brain homogenate as the source of AChE. The efficacy of K203 was compared with commercially available oximes; pralidoxime, obidoxime and asoxime (HI-6)...
February 21, 2018: BMC Pharmacology & Toxicology
https://www.readbyqxmd.com/read/29421945/cytotoxicity-of-acetylcholinesterase-reactivators-evaluated-in-vitro-and-its-relation-to-their-structure
#4
Lubica Muckova, Jaroslav Pejchal, Petr Jost, Nela Vanova, David Herman, Daniel Jun
The development of acetylcholinesterase reactivators, i.e., antidotes against organophosphorus poisoning, is an important goal of defense research. The aim of this study was to compare cytotoxicity and chemical structure of five currently available oximes (pralidoxime, trimedoxime, obidoxime, methoxime, and asoxime) together with four perspective oximes from K-series (K027, K074, K075, and K203). The cytotoxicity of tested substances was measured using two methods - colorimetric 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-tetrazolium bromide assay and impedance based real-time cytotoxicity assay - in three different cell lines (HepG2, ACHN, and NHLF)...
February 9, 2018: Drug and Chemical Toxicology
https://www.readbyqxmd.com/read/29363292/acute-intoxications-among-turkish-children
#5
Baran S Kizilyildiz, Kamuran Karaman, Selvi Özen, Abdurrahman Üner
BACKGROUND: The aim of this study was to investigate characteristics, outcomes and clinical features of acute intoxications among children in Van region of Turkey. METHODS: All cases with a diagnosis of acute intoxication admitted to the Pediatric Emergency Department of the Yüzüncü Yıl University of Van from June 1, 2010 to November 30, 2011 were evaluated. We retrospectively examined the medical records for demographical and etiological characteristics of patients below 17 years of age...
February 2018: Minerva Pediatrica
https://www.readbyqxmd.com/read/29164527/correction-to-a-primer-on-nerve-agents-what-the-emergency-responder-anesthesiologist-and-intensivist-needs-to-know
#6
Keith Candiotti
In the article entitled: "A primer on nerve agents: what the emergency responder, anesthesiologist, and intensivist needs to know" published in the October 2017 issue of the Journal, Can J Anesth 2017; 64: 1059-1070, two doses in Table 3 contained errors and have now been corrected (and highlighted in bold) in the revised table herein. In the table on page 1064, next to "Pralidoxime/Obidoxime/HI-6", the second column should read: "Pralidoxime- Mild cases: 1-2 g iv over 5-10 min or im"...
January 2018: Canadian Journal of Anaesthesia, Journal Canadien D'anesthésie
https://www.readbyqxmd.com/read/29129799/post-exposure-treatment-with-the-oxime-rs194b-rapidly-reactivates-and-reverses-advanced-symptoms-of-lethal-inhaled-paraoxon-in-macaques
#7
Yvonne J Rosenberg, Jerry Wang, Tara Ooms, Narayanan Rajendran, Lingjun Mao, Xiaoming Jiang, Jonathan Lees, Lori Urban, Jeremiah D Momper, Yadira Sepulveda, Yan-Jye Shyong, Palmer Taylor
Fatalities from organophosphate (OP) insecticide result from both occupational and deliberate exposure; significantly impacting human health. Like nerve agents, insecticides are neurotoxins which target and inhibit acetylcholinesterases (AChE) in central and peripheral synapses in the cholinergic nervous system. Post-exposure therapeutic countermeasures generally include administration of atropine with a pyridinium aldoxime e.g. pralidoxime, to reactivate the OP-inhibited AChE. However, commonly used oximes inefficiently cross the bloodbrain barrier and are rapidly cleared and their benefit is debated...
November 9, 2017: Toxicology Letters
https://www.readbyqxmd.com/read/29129798/the-efficacy-of-hi-6-dms-in-a-sustained-infusion-against-percutaneous-vx-poisoning-in-the-guinea-pig
#8
C Whitmore, A R Cook, T Mann, M E Price, E Emery, N Roughley, D Flint, S Stubbs, S J Armstrong, H Rice, J E H Tattersall
Post-exposure nerve agent treatment usually includes administration of an oxime, which acts to restore function of the enzyme acetylcholinesterase (AChE). For immediate treatment of military personnel, this is usually administered with an autoinjector device, or devices containing the oxime such as pralidoxime, atropine and diazepam. In addition to the autoinjector, it is likely that personnel exposed to nerve agents, particularly by the percutaneous route, will require further treatment at medical facilities...
November 10, 2017: Toxicology Letters
https://www.readbyqxmd.com/read/29098328/effect-of-six-oximes-on-acutely-anticholinesterase-inhibitor-induced-oxidative-stress-in-rat-plasma-and-brain
#9
Evica Antonijevic, Jelena Kotur-Stevuljevic, Kamil Musilek, Andrea Kosvancova, Kamil Kuca, Danijela Djukic-Cosic, Vesna Spasojevic-Kalimanovska, Biljana Antonijevic
Beside the key inhibition of acetylcholinesterase (AChE), involvement of oxidative stress in organophosphate (OP)-induced toxicity has been supported by experimental and human studies. On the other hand, according to our best knowledge, possible antioxidant properties of oximes, the only causal antidotes to OP-inhibited AChE, have been examined only by a few studies. Thus, we have determined the effect of four conventional (obidoxime, trimedoxime, pralidoxime, asoxime) and two promising experimental oximes (K027, K203) on dichlorvos (DDVP)-induced oxidative changes in vivo...
November 2, 2017: Archives of Toxicology
https://www.readbyqxmd.com/read/29096055/unusual-double-beckmann-fragmentation-reaction-under-physiological-conditions
#10
Lin-Na Xie, Chun-Hua Huang, Dan Xu, Feng Li, Jun-Ge Zhu, Chen Shen, Bo Shao, Hui-Ying Gao, Balaraman Kalyanaraman, Ben-Zhan Zhu
Pyridinium aldoximes, which are best-known as therapeutic antidotes for organophosphorus chemical warfare nerve-agents and pesticides, have been found to markedly detoxify polyhalogenated quinones, which are a class of carcinogenic intermediates and recently identified disinfection byproducts in drinking water. However, the exact chemical mechanism underlying this detoxication remains unclear. Here we demonstrate that pralidoxime can remarkably facilitate the dechlorination/hydroxylation of the highly toxic tetrachloro-1,4-benzoquinone in two-consecutive steps to generate the much less toxic 2,5-dichloro-3,6-dihydroxy-1,4-benzoquonine, with rate enhancements of up to 180 000-times...
December 15, 2017: Journal of Organic Chemistry
https://www.readbyqxmd.com/read/29091431/application-of-the-ugi-multicomponent-reaction-in-the-synthesis-of-reactivators-of-nerve-agent-inhibited-acetylcholinesterase
#11
Martijn C de Koning, Marloes J A Joosen, Franz Worek, Florian Nachon, Marco van Grol, Steven D Klaassen, Duurt P W Alkema, Timo Wille, Hans M de Bruijn
Recently, a new class of reactivators of chemical warfare agent inhibited acetylcholinesterase (AChE) with promising in vitro potential was developed by the covalent linkage of an oxime nucleophile and a peripheral site ligand. However, the complexity of these molecular structures thwarts their accessibility. We report the compatibility of various oxime-based compounds with the use of the Ugi multicomponent reaction in which four readily accessible building blocks are mixed together to form a product that links a reactivating unit and a potential peripheral site ligand...
November 22, 2017: Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/29081098/-clinical-effect-of-alanyl-glutamine-in-the-treatment-of-patients-with-gastrointestinal-function-obstacle-caused-by-severe-phorate-poisoning
#12
Z K Yu, Z J Gong, X D Jian, A J Qu
Objective: To observe the therapeutic efficacy of alanyl glutamine injection on patients with gastrointestinal function obstacle caused by severe phorate poisoning. Methods: A total of 80 eligible patients with gastrointestinal function obstacle caused by severe phorate poisoning were randomly divided into the control group (n=40) and treatment group (n=40) . The control group was treated with the conventional therapy, which included forbidden diet, atropine, pralidoxime iodide, anti-inflammatory, albumin infusion, ω-3 fish oil fat emulsion, protection of organs function, blood perfusion, and Fat Emulsion, Amino Acids (17) and Glucose Injection...
July 20, 2017: Chinese Journal of Industrial Hygiene and Occupational Diseases
https://www.readbyqxmd.com/read/29062551/-in-vitro-cysteine-reactivates-organophosphate-insecticide-dichlorvos-inhibited-human-cholinesterases
#13
Hamidreza Mohammadi, Jafar Jalilian, Mohammad Y Karimi, Seyed V Shetab-Boushehri
OBJECTIVES: Organophosphate (OP) pesticides inhibit both red blood cell (RBC) and plasma cholinesterases (ChEs). Oximes, especially pralidoxime (2-PAM), are widely used as antidotes to treat OP poisoning. In addition, N-acetylcysteine (NAC) is sometimes used as an adjuvant antidote. The current study aimed to assess the feasibility of using NAC as a single therapeutic agent for OP poisoning in comparison to in vitro 2-PAM. METHODS: This study was carried out at the Razi Drug Research Center of Iran University of Medical Sciences, Tehran, Iran, between April and September 2014...
August 2017: Sultan Qaboos University Medical Journal
https://www.readbyqxmd.com/read/29024789/in-vitro-pharmacological-characterization-of-the-bispyridinium-non-oxime-compound-mb327-and-its-2-and-3-regioisomers
#14
K V Niessen, T Seeger, S Rappenglück, T Wein, G Höfner, K T Wanner, H Thiermann, F Worek
The primary toxic mechanism of organophosphorus compounds, i.e. nerve agents or pesticides, is based on the irreversible inhibition of acetylcholinesterase. In consequence of the impaired hydrolysis, the neurotransmitter acetylcholine accumulates in cholinergic synapses and disturbs functional activity of nicotinic and muscarinic acetylcholine receptors by overstimulation and subsequent desensitization. The resulting cholinergic syndrome will become acute life-threatening, if not treated adequately. The current standard treatment, consisting of administration of a competitive mAChR antagonist (e...
October 9, 2017: Toxicology Letters
https://www.readbyqxmd.com/read/29023426/nanometric-mil-125-nh%C3%A2-metal-organic-framework-as-a-potential-nerve-agent-antidote-carrier
#15
Sérgio M F Vilela, Pablo Salcedo-Abraira, Isabelle Colinet, Fabrice Salles, Martijn C de Koning, Marloes J A Joosen, Christian Serre, Patricia Horcajada
The three-dimensional (3D) microporous titanium aminoterephthalate MIL-125-NH₂ (MIL: Material of Institut Lavoisier) was successfully isolated as monodispersed nanoparticles, which are compatible with intravenous administration, by using a simple, safe and low-cost synthetic approach (100 °C/32 h under atmospheric pressure) so that for the first time it could be considered for encapsulation and the release of drugs. The nerve agent antidote 2-[(hydroxyimino)methyl]-1-methyl-pyridinium chloride (2-PAM or pralidoxime) was effectively encapsulated into the pores of MIL-125-NH₂ as a result of the interactions between 2-PAM and the pore walls being mediated by π-stacking and hydrogen bonds, as deduced from infrared spectroscopy and Monte Carlo simulation studies...
October 12, 2017: Nanomaterials
https://www.readbyqxmd.com/read/28959515/acute-renal-failure-due-to-organophosphate-poisoning-a-case-report
#16
Rizwan Zafar, Kamran Munawar, Adeel Nasrullah, Shujaul Haq, Haider Ghazanfar, Abu Baker Sheikh, Ali Y Khan
Organophosphate (OP) poisoning is a commonly seen condition in many countries. OP poisoning classically presents with symptoms of cholinergic excess. It can rarely affect other organ systems but when it does, it can worsen a patient's overall prognosis. We present a case of a 23-year-old man with an extremely rare case of acute kidney injury due to OP, who was successfully treated with a combination of hemodialysis, atropine and pralidoxime days after OP poisoning with reservations on the aging process.
July 27, 2017: Curēus
https://www.readbyqxmd.com/read/28734368/exploring-pralidoxime-chloride-as-a-universal-electrochemical-probe-for-organophosphorus-pesticides-detection
#17
Qiqi Zheng, Yuan Chen, Kai Fan, Jian Wu, Yibin Ying
An electrochemical method based on non-enzymatic inhibition for the determination of organophosphorus pesticide (OPPs) using pralidoxime chloride (PAM-Cl) as a universal electrochemical probe was reported. Cyclic voltammetry was performed to characterize the redox properties of pralidoxime and OPPs. Differential pulse voltammetry (DPV) was carried out to analyze the influence of anion (chloride and iodide ions), to optimize the pH of testing condition, and to explore the relationship between pralidoxime and OPPs...
August 22, 2017: Analytica Chimica Acta
https://www.readbyqxmd.com/read/28722512/in-silico-and-in-vitro-evaluation-of-two-novel-oximes-k378-and-k727-in-comparison-to-k-27-and-pralidoxime-against-paraoxon-ethyl-intoxication
#18
Maria Arshad, Muhammad Qaiser Fatmi, Kamil Musilek, Alamdar Hussain, Kamil Kuca, Georg Petroianu, Huba Kalasz, Syed Muhammad Nurulain
Organophosphate (OP) poisoning is a major global health issue; while compounds from this group have been used intensively over the last century, an effective antidote is still lacking. Oxime-type acetylcholinesterase (AChE) reactivators are used to reactivate the OP inhibited AChE. Pralidoxime is the only US Food and Drug Administration approved oxime for therapeutic use but its efficacy has been disappointing. Two novel oximes (K378 and K727) were investigated in silico and in vitro and compared with an experimental oxime (kamiloxime; K-27) and pralidoxime...
January 2018: Toxicology Mechanisms and Methods
https://www.readbyqxmd.com/read/28648599/2-3-butandione-2-monoxime-inhibits-skeletal-myosin-ii-by-accelerating-atp-cleavage
#19
Hideyuki Komatsu, Yuji Koseki, Takeshi Kanno, Shunsuke Aoki, Takao Kodama
2,3-Butandione 2-monoxime (BDM) is a widely used myosin inhibitor with an unclear mode of action. In this report, we investigated the mechanism of BDM oxime group nucleophilic reactivity on the phosphoester bond of ATP. BDM increased the ATPase activity of skeletal myosin subfragment 1 (S1) under conditions in which ATP cleavage is the rate-limiting step (K+ , EDTA-ATPase activity of native S1 and Mg2+ -ATPase activity of trinitrophenylated S1 and partially unfolded S1). Furthermore, the effect of BDM on the S1-bound adenosine 5'-(β,γ-imido) triphosphate (AMPPNP)31 P NMR spectrum suggests that BDM changes the microenvironment around the phosphorus atoms of myosin-bound nucleotide...
August 26, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28644688/intraosseous-administration-of-antidotes-a-systematic-review
#20
REVIEW
Audrée Elliott, Pierre-André Dubé, Amélie Cossette-Côté, Laura Patakfalvi, Eric Villeneuve, Martin Morris, Sophie Gosselin
CONTEXT: Intraosseous (IO) access is an established route of administration in resuscitation situations. Patients with serious poisoning presenting to the emergency department may require urgent antidote therapy. However, intravenous (IV) access is not always readily available. OBJECTIVE: This study reviews the current evidence for IO administration of antidotes that could be used in poisoning. The primary outcome was mortality as a surrogate of efficacy. Secondary outcomes included hemodynamic variables, electrocardiographic variables, neurological status, pharmacokinetics outcomes, and adverse effects as defined by each article...
December 2017: Clinical Toxicology
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